Critical Role for CD103+/CD141+ Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma

Abstract

Intratumoral dendritic cells (DC) bearing CD103 in mice or CD141 in humans drive intratumoral CD8(+) Tcell activation. Using multiple strategies, we identified a critical role for these DC in trafficking tumor antigen to lymph nodes (LN), resulting in both direct CD8(+) Tcell stimulation and antigen hand-off to resident myeloid cells. These effects all required CCR7. Live imaging demonstrated direct presentation to Tcells in LN, and CCR7 loss specifically in these cells resulted in defective LN Tcell priming and increased tumor outgrowth. CCR7 expression levels in human tumors correlate with signatures of CD141(+) DC, intratumoral Tcells, and better clinical outcomes. This work identifies an ongoing pathway to Tcell priming, which should be harnessed for tumor therapies.